Planar and Central Chiral [2.2]Paracyclophanes as Powerful Catalysts for Asymmetric 1,2-Addition Reactions

Abstract

Planar and central chiral [2.2]paracyclophane ligands have been designed and used in the highly enantioselective addition of alkyl, alkenyl, alkynyl and aryl zinc reagents to aldehydes and imines.

1 Why Use [2.2]Paracyclophanes as Chiral Ligands?

2 Synthesis of [2.2]Paracyclophane Ligands

2.1 Preparation and Resolution of FHPC, AHPC and BHPC-Based Imines

2.2 Synthesis of Further Imines Based on FHPC and AHPC

2.3 Synthesis of Chiral Amine Ligands

2.4 1,2-Addition to Imines

2.5 Reductive Amination

2.6 Structural Information on AHPC-Based Imines

2.7 Synthesis of Enantiomerically Pure Thio-Substituted ­Paracyclophanes

2.8 Other Cyclophane-Based Ligands Used for Asymmetric 1,2-Addition Reactions

3 Asymmetric 1,2-Addition Reactions to Aryl Aldehydes

3.1 Initial Considerations

3.2 Mechanistic Investigations

3.3 Reactivity of [2.2]Paracyclophane Ligands

3.4 Asymmetric Addition Reactions to Aromatic Aldehydes: Scope of Substrates

4 Asymmetric Addition Reactions to Aliphatic Aldehydes

5 Addition of Alkenyl Zinc Reagents to Aldehydes

6 Addition of Alkynyl Zinc Reagents to Aldehydes

7 Addition of Phenylzinc to Aldehydes

8 Asymmetric Addition Reactions to Imines

9 Asymmetric Addition Reactions on Solid Supports

10 Conclusions and Outlook

11 Abbreviations

Key words

asymmetric catalysis - ligands - paracyclophanes - zinc - nucleophilic additions

References

• 1 Knowles WS. Sabacky M. J. Chem. Soc., Chem. Commun.  1968,  1445 
• 2 Kagan HB. Dang TP. J. Am. Chem. Soc.  1972,  94:  6429 
• 3 Noyori R. Science  1990,  248:  1194 
• 4a Knowles WS. Angew. Chem. Int. Ed.  2002,  41:  1996 ; Angew. Chem. 2002, 114, 2096
• 4b Noyori R. Angew. Chem. Int. Ed.  2002,  41:  2008 ; Angew. Chem. 2002, 114, 2108
• 4c Sharpless KB. Angew. Chem. Int. Ed.  2002,  41:  2024 ; Angew. Chem. 2002, 114, 2126
• 5 Stinson SC. Chem. Eng. News  2001,  79:  45 
• 6a Reich HJ. Cram DJ. J. Am. Chem. Soc.  1969,  91:  3527 
• 6b Cram DJ. Steinberg H. J. Am. Chem. Soc.  1951,  73:  5691 
• 7a Pye PJ. Rossen K. Reamer RA. Tsou NN. Volante RP. Reider PJ. J. Am. Chem. Soc.  1997,  119:  6207 
• 7b Rossen K. Reamer RA. Volante RP. Reider PJ. Tetrahedron Lett.  1998,  39:  4441 
• 7c Rossen K. Pye PJ. Maliakal A. Volante RP. J. Org. Chem.  1997,  62:  6462 
• 8 Gibson S. Knight JD. Org. Biomol. Chem.  2003,  1:  1256 
• 9 Bräse S. Lauterwasser F. Ziegert RE. Adv. Synth. Catal.  2003,  345:  869 
• 10 Helmchen G. Pfaltz A. Acc. Chem. Res.  2000,  33:  336 
• 11 Vetter AH. Berkessel A. Tetrahedron Lett.  1998,  39:  1741 
• 12a Rozenberg V. Kharitonov V. Antonov D. Sergeeva E. Aleshkin A. Ikonnikov N. Orlova S. Belokon Y. Angew. Chem., Int. Ed. Engl.  1994,  33:  91 ; Angew. Chem. 1994, 106, 106
• 12b Antonov D. Belokon YN. Ikonnikov NS. Orlova SA. Pisaevsky AP. Raevski NI. Rozenberg VI. Sergeeva EV. Struchkov YT. Tararov VI. Vorontsov EV. J. Chem. Soc., Perkin Trans. 1  1995,  1873 
• 13 Rozenberg V. Danilova T. Sergeeva E. Vorontsov E. Starikova Z. Lysenko K. Belokon Y. Eur. J. Org. Chem.  2000,  3295 
• 14a Pastor SD. Togni A. J. Am. Chem. Soc.  1989,  111:  2333 
• 14b Togni A. Pastor SD. J. Org. Chem.  1990,  55:  1649 
• 14c Pastor SD. Togni A. Helv. Chim. Acta  1991,  74:  905 
• 14d

  The term ‘Chiral Cooperativity’ was used by Pastor and Togni to describe positive interaction of different chiral moieties surpassing their mere addition. The case of diminishing was not investigated by the authors. Therefore they used ‘not cooperative’ in the case of a ‘mismatched pair’.

• 15a Masamune S. Choy W. Petersen JS. Sita LR. Angew. Chem., Int. Ed. Engl.  1985,  24:  1 ; Angew. Chem. 1985, 97, 1
• 15b Heathcock CH. White CT. J. Am. Chem. Soc.  1979,  101:  7076 
• 15c Horeau A. Kagan H.-B. Vigneron J.-P. Bull. Soc. Chim. Fr.  1968,  3795 
• 16a Hayashi T. Tajika M. Tamao K. Kumada M. J. Am. Chem. Soc.  1976,  98:  3718 
• 16b Hayashi T. Konishi M. Fukushima M. Mise T. Kagotani M. Tajika M. Kumada M. J. Am. Chem. Soc.  1982,  104:  180 
• 17a Bolm C. Muniz-Fernández K. Seger A. Raabe G. Günther K. J. Org. Chem.  1998,  63:  7860 
• 17b Bolm C. Muniz K. Hildebrand JP. Org. Lett.  1999,  1:  491 
• For studies on chiral cooperativity in axial- and central-chiral ligands, see:
• 18a Buisman GJH. van der Veen LA. Klootwijk A. de Lange WGI. Kamer PCJ. van Leeuwen PWNM. Vogt D. Organometallics  1997,  16:  2929 
• 18b Cserépi-Szûcs S. Tóth I. Párkányi L. Bakos J. Tetrahedron: Asymmetry  1998,  9:  3135 
• 18c Cserépi-Szûcs S. Huttner G. Zsolnai L. Szölõsy A. Hegedüs C. Bakos J. Inorg. Chim. Acta  1999,  296:  222 
• 19a Hopf H. Barrett DG. Liebigs Ann.  1995,  449 
• 19b Cipiciani A. Fringuelli F. Mancini V. Piermatti O. Pizzo F. Ruzziconi R. J. Org. Chem.  1997,  62:  3744 
• 19c Pamperin D. Schulz C. Hopf H. Syldatk C. Pietzsch M. Eur. J. Org. Chem.  1998,  1441 
• 19d Rozenberg V. Danilova T. Sergeeva E. Vorontsov E. Starikova Z. Korlyukov A. Hopf H. Eur. J. Org. Chem.  2002,  468 
• 20a Hoffmann RW. Ditrich K. Synthesis  1983,  107 
• 20b Krohn K. Rieger H. Hopf H. Barrett D. Jones PG. Doring D. Chem. Ber.  1990,  123:  1729 
• 21 Dahmen S. Bräse S. Tetrahedron: Asymmetry  2001,  12:  2845 
• 22 Sergeeva EV. Rozenberg VI. Vorontsov EV. Danilova TI. Starikova ZA. Yanovsky AI. Belokon YN. Hopf H. Tetrahedron: Asymmetry  1996,  7:  3445 
• 23 Kane VV. Gerdes A. Grahn W. Ernst L. Dix I. Jones PG. Hopf H. Tetrahedron Lett.  2001,  42:  373 
• 24a Cipiciani A. Fringuelli F. Mancini V. Piermatti O. Scappini AM. Ruzziconi R. Tetrahedron  1997,  53:  11853 
• 24b Pamperin D. Schulz C. Hopf H. Syldatk C. Pietzsch M. Eur. J. Org. Chem.  1998,  1441 
• 26 Still IWJ. Natividad-Preyra R. Toste FD. Can. J. Chem.  1999,  77:  113 
• 27 Miranda EI. Díaz MJ. Rosado I. Soderquist JA. Tetrahedron Lett.  1994,  50:  3221 
• 28 Wipf P. Kendall C. Chem.-Eur. J.  2002,  8:  1778 
• 29 Danilova T. Rozenberg V. Vorontsov EV. Starikova Z. Hopf H. Tetrahedron: Asymmetry  2003,  14:  1375 
• 30 Danilova T. Rozenberg VI. Sergeeva EV. Starikova ZA. Bräse S. Tetrahedron: Asymmetry  2003,  14:  2013 
• 33 Dahmen S. PhD Thesis   RWTH Aachen: 2002. 
• 38a Goldfuss B. Houk KN. J. Org. Chem.  1998,  63:  8998 
• 38b Goldfuss B. Steigelmann M. Khan SI. Houk KN. J. Org. Chem.  2000,  65:  77 
• 39 Rasmussen T. Norrby P.-O. J. Am. Chem. Soc.  2001,  123:  2464 
• 40a Kitamura M. Suga S. Oka H. Noyori R. J. Am. Chem. Soc.  1998,  120:  9800 
• 40b

  Dahmen, S.; Lauterwasser, F.; Vanderheiden, S.; Bräse, S. unpublished.

• 40c Wipf P. Pierce JG. Wang X. Tetrahedron: Asymmetry  2003,  14:  3605 ; and references cited therein
• 41 Dahmen S. Bräse S. Chem. Commun.  2002,  26 
• 42 Nugent WA. Org. Lett.  2002,  4:  2133 
• 43 Höfener S. Lauterwasser F. Bräse S. Adv. Synth. Catal.  2004,  346:  755 
• 44 Dahmen S. Bräse S. unpublished
• 46a Oppolzer W. Radinov RN. Tetrahedron Lett.  1988,  29:  5645 
• 46b Oppolzer W. Radinov RN. Tetrahedron Lett.  1991,  32:  5777 
• 47a Noyori R. Kitamura M. Angew. Chem., Int. Ed. Engl.  1991,  30:  49 
• 47b Kitamura M. Suga S. Kawai K. Noyori R. J. Am. Chem. Soc.  1986,  108:  6071 
• 48a Oppolzer W. Radinov RN. Helv. Chim. Acta  1992,  75:  170 
• 48b This reaction was recently extended to intramolecular cyclization reactions: Oppolzer W. Radinov RN. El-Sayed E. J. Org. Chem.  2001,  66:  4766 
• The addition of vinylzinc has also been studied:
• 49a von dem Bussche-Hünnefeld JL. Seebach D. Tetrahedron  1992,  48:  5719 
• 49b Soai K. Takahashi K. J. Chem. Soc., Perkin Trans. 1  1994,  1257 
• 49c Shibata T. Nakatsui K. Soai K. Inorg. Chim. Acta  1999,  296:  33 
• 50a Wipf P. Xu W. Tetrahedron Lett.  1994,  35:  5197 
• 50b Wipf P. Xu W. Org. Synth.  1997,  74:  205 
• 50c Wipf P. Ribe S. J. Org. Chem.  1998,  63:  6454 
• 51 Dahmen S. Bräse S. Org. Lett.  2001,  3:  4119 
• 54a Nehl H. Scheidt W. J. Organomet. Chem.  1985,  289:  1 
• 54b Mynott R. Gabor B. Lehmkuhl H. Doering I. Angew. Chem., Int. Ed. Engl.  1985,  24:  335 
• 55a Bolm C. Hermanns N. Hildebrand JP. Muniz K. Angew. Chem. Int. Ed.  2000,  39:  3465 ; Angew. Chem. 2000, 112, 3607
• 55b Blacker J. In Proceedings of the 3rd International Conference on the Scale Up of Chemical Processes   Laird T. Scientific Update; Mayfieldn / East Sussex / Great Britain: 1998. 
• 56 Alvaro G. Pacioni P. Savoia D. Chem.-Eur. J.  1997,  3:  726 
• 57 Modern Acetylene Chemistry   Stang PJ. Diederich F. VCH; Weinheim: 1995. 
• 58 For a recent review, see: Pu L. Tetrahedron  2003,  59:  9873 
• 59 Ishizaki M. Hoshino O. Tetrahedron: Asymmetry  1994,  5:  1901 
• 60a Frantz DE. Fässler R. Carreira EM. J. Am. Chem. Soc.  2000,  122:  1806 
• 60b Boyall D. López F. Sasaki H. Frantz D. Carreira EM. Org. Lett.  2000,  2:  4233 
• 60c Frantz DE. Fässler R. Tomooka CS. Carreira EN. Acc. Chem. Res.  2000,  33:  373 
• 60d Anand NK. Carreira EN. J. Am. Chem. Soc.  2001,  123:  9687 
• 62 Xu M.-H. Pu L. Org. Lett.  2002,  4:  4555 
• 63 Bolm C. Rudolph J. J. Am. Chem. Soc.  2002,  124:  14850 
• For selected references in this field, see:
• 66a Bolm C. Hildebrand JP. Muniz K. Hermanns N. Angew. Chem. Int. Ed.  2001,  40:  3284 ; Angew. Chem. 2001, 113, 3382
• 66b Bolm C. Rudolph J. J. Am. Chem. Soc.  2002,  124:  14850 
• 66c Rudolph J. Schmidt F. Bolm C. Adv. Synth. Catal.  2004,  346:  867 
• For selected APIs, see: (S)-Carbinoxamine:
• 67a Roszowski AP. Govier WM. Pharmakologist  1959,  1:  60 
• 67b Hunt JH. J. Chem. Soc.  1961,  2228 
• 67c Barouh V. Dall H. Patel D. Hite G. J. Med. Chem.  1971,  14:  834 
• 67d James MNG. Williams GJB. Can. J. Chem.  1974,  52:  1872 
• 67e

  (R)-Neobenodin and (R)-orphenadrin:

• 67f Casy AF. Drake AF. Ganellin CR. Mercer AD. Chirality  1992,  4:  356 
• 67g van der Stelt C. Heus WJ. Nauta WT. Arzneim.-Forsch.  1969,  19:  2010 
• 67h Rekker RF. Timmerman H. Harms AF. Nauta WT. Arzneim.-Forsch.  1971,  21:  688 
• 68a Corey EJ. Helal CJ. Tetrahedron Lett.  1995,  36:  9153 
• 68b Corey EJ. Helal CJ. Tetrahedron Lett.  1996,  37:  4837 
• 68c Corey EJ. Helal CJ. Tetrahedron Lett.  1996,  37:  5675 
• 68d Corey EJ. Helal CJ. Angew. Chem. Int. Ed.  1998,  37:  1986 ; Angew. Chem. 1998, 110, 2092
• 69a Okhuma T. Koizumi M. Ikehira H. Yokozawa T. Noyori R. Org. Lett.  2000,  2:  659 
• 69b Noyori R. Okhuma T. Pure Appl. Chem.  1999,  71:  1493 
• 70 Hermanns N. PhD Thesis   RWTH; Aachen: 2002. 
• 71 Rudolph J. PhD Thesis   RWTH; Aachen: 2004. 
• 72a Dahmen S. Bräse S. J. Am. Chem. Soc.  2002,  124:  5940 
• 72b Hermanns N. Dahmen S. Bolm C. Bräse S. Angew. Chem. Int. Ed.  2002,  41:  3692 ; Angew. Chem. 2002, 114, 3844
• 74 Knepper K. Ziegert RE. Bräse S. Tetrahedron  2004,  60:  8591 

25

Kreis, M. unpublished results.

31

The transfer of the planar cylopentadienyl moiety of the ferrocene to benzenederivatives as done by Bolm et al. is risky, because of the change of the ortho-angle from 72° for the ferrocene to 60° for the benzenederivatives. These changes in the molecule geometry make it extremely difficult to derive the exact nature of the transition state from the one of the ferrocene.

32

To give the reader the opportunity to compare the results of the catalysis directly with the ligand structure, we do this without a detailed summary of the reactions. Further in this chapter, we will only show the catalyst and its results in the diethylzinc addition to benzaldehyde with the conditions as shown in Scheme [12] .

34

Lauterwasser, F. unpublished results.

35

Energy minimization of the corresponding conformers were done with Chem3D Pro and CS MOPAC Pro.

36

In a PM3 calculation of the conformers done by J. Rudolph with the program Spartan 2001 (Wavefunction Inc., California) the results of the MNDO-analysis werde confirmed, resulting in conformer A as the conformer with the lowest energy. Although the differences in energy by this method are only 5 kcal/mol and therefore a bit lower as with MNDO, they are still high enough to make any consideration of the conformer B superfluous. (1 kcal = 4.1868 kJ).

37

The energy differences of the µ-O structures are only between 1-3 kcal/mol.

45

Allyl alcohols are substrates for, e.g., cyclopropanation reactions, aziridination reactions, ene-reactions, epoxidations, dihydroxylations, methoxy selenations, iodo hydroxylations, brominations, and allylic substitution reactions.

52

Using these modifications, the aldehyde could be added in one portion, which is a significant practical improvement over the original Oppolzer protocol, where the aldehyde had to be added over a period of 20 min to obtain high enantioselectivities.

53

The absolute configuration was assigned by comparison of the optical rotation with the literature known compounds (S)-1-(4-chlorophenyl)hept-2-en-1-ol and (S)-1-phenylnon-2-en-1-ol, respectively, and the assumption of a unanimous reaction pathway for all other aldehyde substrates. The absolute configuration of the allyl alcohol products 51 is consistent with the induction observed in the diethylzinc addition to aldehydes with the ligands 5a and 6a.

61

Zn(OTf)₂ is ten times more expensive than diethylzinc: Zn(OTf)₂: 10 g 46.80 $ ( = 1 $/mmol), Et₂Zn in hexane: 100 g (810 mmol) 80.90 $ (= 0.1 $/mmol). Prices taken from Acros Organics.

64

This behavior is untypical for mixed zinc species. The equilibrium could be influenced by the very low solubility of the dialkynylzinc reagents.

65

The clear supernant solution gives rise to the ethylation product in >80% yield.

73

Bräse, S.; Dahmen, S.; Vogt, H. to be submitted.